Jurnal

Copper containing intra-uterine devices versus depot
progestogens for contraception (Review)

Hofmeyr GJ, Singata M, Lawrie TA
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2010, Issue 6
http://www.thecochranelibrary.com
Copper containing intra-uterine devices versus depot progestogens for contraception (Review)
Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1 HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4 OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4 METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6 RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
7 DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8 AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8 ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11 CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13 DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 IUCD versus depot progestogen, Outcome 1 Pregnancy. . . . . . . . . . . . 14
Analysis 1.2. Comparison 1 IUCD versus depot progestogen, Outcome 2 Discontinuation of allocated method. . . 15
Analysis 1.3. Comparison 1 IUCD versus depot progestogen, Outcome 3 HIV disease progression: CD4 < 200. . . 16
Analysis 1.4. Comparison 1 IUCD versus depot progestogen, Outcome 4 HIV disease progression: death. . . . . 17
Analysis 1.5. Comparison 1 IUCD versus depot progestogen, Outcome 5 HIV disease progression (CD4 < 200 or death). 17
Analysis 1.6. Comparison 1 IUCD versus depot progestogen, Outcome 6 Pelvic inammatory disease. . . . . . 18
18 HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18 CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19 DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19 SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
i Copper containing intra-uterine devices versus depot progestogens for contraception (Review)
[Intervention Review]
Copper containing intra-uterine devices versus depot
progestogens for contraception
G Justus Hofmeyr
1
, Mandisa Singata
2
, Theresa A Lawrie
3
1
Department of Obstetrics and Gynaecology, East London Hospital Complex, University of the Witwatersrand, University of Fort
Hare, Eastern Cape Department of Health, East London, South Africa.
2
Effective Care Research Unit, University of the Witwater-
srand/University of Fort Hare/East London Hospital complex, East London, South Africa.
3
Effective Care Research Unit, University
of the Witwatersrand/University of Fort Hare/East London Hospital Complex, East London, South Africa
Contact address: G Justus Hofmeyr, Department of Obstetrics and Gynaecology, East London Hospital Complex, University of the
Witwatersrand, University of Fort Hare, Eastern Cape Department of Health, Frere and Cecilia Makiwane Hospitals, Private Bag X
9047, East London, Eastern Cape, 5200, South Africa. gjh@global.co.za.
Editorial group: Cochrane Fertility Regulation Group.
Publication status and date: New, published in Issue 6, 2010.
Review content assessed as up-to-date: 7 February 2010.
Citation: Hofmeyr GJ, Singata M, Lawrie TA. Copper containing intra-uterine devices versus depot progestogens for contraception.
Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD007043. DOI: 10.1002/14651858.CD007043.pub2.
A B S T R A C T
Background
Highly effective contraception is essential to reduce unintended pregnancies and the effect these have on individuals, society and public
health resources. Intrauterine devices (IUDs) and depot progestogens are two commonly used long-acting, reversible contraceptive
methods with different risk and benet proles.
Objectives
To compare the contraceptive and non-contraceptive benets and risks of using the copper-containing IUD versus depot progestogens
for contraception.
Search strategy
In June 2009 we searched the Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Central Register of Controlled
Trials, Pubmed, Popline, Clinical Trials.gov, the Current Controlled Trials metaRegister, EMBASE and LILACS, and contacted study
authors.
Selection criteria
Randomized trials comparing women using copper-containing IUDs with women using depot progestogens.
Data collection and analysis
We assessed eligibility and trial quality, extracted and double-entered data.
Main results
Two studies were included in the review. In the one study in HIV infected women, the IUD was compared with depot progestogen
or the oral contraceptive, according to the womens choice. As the majority of women chose depot progestogen, we have included this
study in the review, within a mixed hormonal contraception sub-group.
1 Copper containing intra-uterine devices versus depot progestogens for contraception (Review)
Overall, the copper IUD was more effective than depot progestogens/hormonal contraception at preventing pregnancy (risk ratio (RR)
0.45; 95% condence interval (CI) 0.24 to 0.84). HIV disease progression was reduced in the IUD group (RR 0.58; 95% CI 0.39 to
0.87). There was no signicant difference in pelvic inammatory disease rates between the two groups. Discontinuation of the allocated
method was less frequent with the IUD in one study, and less frequent with hormonal contraception in the other study (in which
women were allowed to switch between various hormonal methods).
Authors conclusions
Inthe populations studied, the IUDwas more effective thanhormonal contraceptionwith respect to pregnancy prevention. High quality
research is urgently needed to compare the effects, if any, of these two commonly used contraception methods on HIV acquisition/
seroconversion and HIV/AIDS disease progression.
P L A I N L A N G U A G E S U M M A R Y
Copper IUDs versus long-acting hormone injections and implants for contraception
Reversible, longterm contraception is relied on by millions of women to prevent unwanted pregnancy. Two very common methods of
pregnancy prevention are the use of a copper-containing intrauterine device (IUD) or an injection of a progestogen hormone.
We reviewed studies that compared these two highly effective methods and found the IUD to be better at preventing pregnancy
than depot medroxyprogesterone acetate (DMPA). Relevant to HIV positive women are the results of one small trial that found that
women using the IUD for contraception where less likely to experience a worsening of their HIV disease than those using hormonal
contraception. A large, high quality study is urgently needed to shed light on these ndings.
B A C K G R O U N D
Unintended pregnancies have important physical, emotional and
social consequences for individuals and society, place a burden on
health services and contribute to maternal and perinatal mortality.
There is considerable evidence to show that the Millennium De-
velopment Goal to reduce maternal mortality will not be achiev-
able with current levels of population growth in the least devel-
oped countries and regions (APPG 2007; Campbell 2007).
As women respond differently to the various methods of contra-
ception, the utilization of contraceptive services is directly related
to the range of contraceptive choices offered. In many areas, the
use of the intrauterine contraceptive device (IUD) has virtually
disappeared, and contraceptive service providers are not trained in
its use.
Injectable progestogen contraceptives (depot progestogen) ac-
count for a large proportion of modern-day contraception use in
many countries, including South Africa (80%), Indonesia (67%),
Peru (55%), Kenya (42%) and Nepal (40%) (Ortayli 2006). In
Uzbekistan, however, most women use the IUD (Barrett 2007).
Depot progestogen contraceptives
Injectable progestogen contraceptives are acceptable to many
women, and are considered to have several advantages:
1. convenience
2. infrequent dosage (two or three monthly)
3. adherence not related to intercourse
4. protection against endometrial cancer
5. some protection against pelvic infection
However, they are considered to have disadvantages which may
lead to discontinuation and unwanted pregnancies. These include
the following:
1. irregular vaginal bleeding
2. amenorrhoea (considered an advantage by some women)
3. delayed return of fertility
4. nausea
5. weight gain
6. loss of bone density
7. the need to remember the repeat injections
8. dependence on supplies at clinics
9. difculty of knowing when to stop use in perimenopausal
women
In a Cochrane systematic review, the rate of discontinuing depot
progestogen contraception within 12 months was found to be
49% for depot MPA and 48% for norethisterone enanthate, the
main reason for which was menstrual disturbances (Draper 2006).
In a double-blind, placebo controlled study, depot progestogen
contraception (norethisterone enanthate) in the postpartum pe-
riod was associated with increased depression and reduced serum
estradiol and progesterone levels (Lawrie 1998). It is possible that
reduced estrogen levels may result in thinning of the vaginal ep-
itheliumand that exogenous steroids may cause humoral and cell-
mediated immunological changes, increasing the risk of genital
tract infection. A recent review of highly effective contraception
(Morrison 2009) that included two large prospective cohort stud-
ies (Morrison 2007; Myer 2007) found no association between
DMPA and HIV acquisition in the general population, although
data was equivocal for high-risk groups (e.g. sex workers). Regard-
ing sexually transmitted infections (STIs), the review found some
evidence to support an increased risk of chlamydial infection, but
not gonorrhoea.
The copper IUD
The copper IUD is also considered to have advantages and disad-
vantages.
Advantages include the following:
1. no hormonal effects
2. no amenorrhoea
3. immediate return to fertility on removal
4. single insertion lasts from ve to ten years, depending on
the type of device
5. may be left in place until after the menopause (Bhathena
2006; Sivin 2007)
6. reduced risk of hemorrhagic stroke compared with
hormonal contraceptive use (Li 2006)
7. lower rates of discontinuation than other contraceptive
methods (Youssef 2005)
8. in a recent randomized trial in HIV infected women, the
IUD was found to be a suitable contraceptive (Stringer 2007)
9. IUD use does not increase the risk of ectopic pregnancy
(Barnhart 2006)
10. adherence is not intercourse related
Disadvantages include the following:
1. initial insertion, which requires a skilled provider, and may
be painful
2. increased menstrual ow and menstrual pain in some
women
3. rare complications such as uterine perforation and
migration, which may be provider-related (El-Hefnawy 2007)
4. an increased risk of pelvic infection in the initial 30 days
following insertion (Mohllajee 2006)
Insertion of the IUD immediately following pregnancy (meaning
within48 hours) (Grimes 2003; WHO2009) or abortion(Grimes
2004) appears safe, but the expulsion rate appears to be higher
thanfor interval insertion. Copper IUDs canbe tted immediately
after both surgical and medical abortion (Grimes 2004).
Nulliparous women (women who have not previously given birth)
may experience more discomfort on insertion and higher rates of
expulsion (Hubacher 2007). However, difcult and failed inser-
tion in nulliparous women has been shown to be reduced with
misoprostol pre-treatment (Sv 2007). Arandomized trial in nul-
liparous women found that IUDs specically designed for nul-
liparous women had lower discontinuation and pregnancy rates
than the standard IUD (Otero-Flores 2003).
Modern intrauterine contraceptive devices (IUDs) are safe, effec-
tive, and quickly reversible long-term contraceptives that require
little attention after insertion. However, safety concerns and pro-
grammatic challenges have held back IUD services in many coun-
tries. For example, declining use of the IUD in Ghana has been
attributed to rumours about adverse effects, and worries about
bleeding and weight loss (Osei 2005). Uptake of the IUDhas been
found to be linked to the quality of contraceptive services (Hong
2006).
Newassessment of research ndings, recently translated into guid-
ance by the World Health Organization, should help reassure
providers that most women can use IUDs safely (Salem 2006). A
case control study has also found that IUD failure was associated
only with a history of previous IUD expulsion, and not with use
of medication, gynecological factors such as broids or polyps, or
previous abortion (Thonneau 2006).
The primary reasons for requesting removal of the IUD are men-
strual bleeding and pain. One randomized trial of prophylac-
tic ibuprofen found no reduction in removal with this treat-
ment (Hubacher 2006), while other randomized trials have found
that the increase in menstrual blood loss with the IUD was
prevented with ibuprofen (Mkrinen 1986), tranexamic acid
(Ylikorkala 1983; Lin 2007) and to a lesser extent diclofenac
sodium (Hubacher 2006). Naproxen was found to be effective in
reducing dysmenorrhea associated with the IUD (Lalos 1983).
Another strategy to reduce complications is use of the frameless
IUD (Wildemeersch 2007). To date, however, evidence of benet
for the frameless IUD over the conventional IUD is limited to
a lower pregnancy rate (though the absolute reduction is small)
(OBrien 2005).
The effectiveness of the IUD with > 250 mm2 copper is equiva-
lent to that of the more expensive progestogen-impregnated IUD,
but with lower rates of expulsion and discontinuation for amenor-
rhea (French 2004). A systematic review found the most effective
framed copper IUD to be the Copper T 380A (Kulier 2006). In a
population-based study in France, the IUD had the lowest failure
rate among contraceptive methods (Moreau 2007).
Several epidemiological studies have found the IUD to be associ-
ated with a reduced risk of endometrial cancer (Tao 2006; Curtis
2007).
The IUD and infection
The main reason limiting the use of the IUD in young women is
the belief that it may cause pelvic infection. Other than during the
immediate post-insertion period, this belief has not been borne
out by research evidence (Meirik 2007). Arecent reviewconcluded
that the use of the IUD is not contraindicated for women with
HIV/AIDS, multiple sexual partners, previous actinomyces col-
onization, most types of broids, or previous ectopic pregnancy.
The review also concluded that the risk to IUD users of develop-
ing pelvic inammatory disease (PID) is similar to women using
no contraception and that IUD use of up to three and a half years
is not associated with decreased fertility (Paladine 2006). A subse-
quent study also conrmed that the use of the IUD is acceptable
in high-risk women with a previous history of STIs (Campbell
2007b).
Pelvic infection in women with an IUD in place responds more
rapidly to treatment if the IUD is removed (Altunyurt 2003). In
one study, use of a stringless IUDwas not shown to reduce the risk
of pelvic infection (Potts 1991). However, in another randomized
trial, leaving the strings inside the uterine cavity was associated
with fewer infections (Pap-Akeson 1992). The threads were easily
retrievedwithout analgesia in84%of womenusing a Retrievette.
Both the Retrievetteand the Emmett thread retriever have been
shown to be highly effective in retrieving missing threads (Bounds
1992). Intrauterine lidocaine may relive pain during retrieval of
lost IUDs (Gney 2007).
A systematic review concluded that the use of prophylactic doxy-
cycline or azithromycin at the time of insertion did not reduce
the risk of infection, which was rare with or without antibiotic
prophylaxis (Grimes 1999). In a trial conducted in Kenya where
rates of genital tract infections were high, there was a trend towards
reduced infection, and a signicantly reduced number of women
returning with problems when doxycycline 200 mg was adminis-
tered at the time of IUD insertion (Sinei 1990). A specic risk of
the IUD is actinomyces infection, which is rare and responds well
to treatment with penicillin (Quercia 2006).
Comparisons of the IUD and hormonal
contraception
A randomized trial of the progestogen-impregnated IUD versus
oral contraception in young nulliparous women found the rate of
discontinuation of the IUD to be somewhat lower than that for
oral contraception(Suhonen 2004). Ina non-randomized study in
Kenya, the rate of discontinuation of the IUDwas lower than that
for depot medroxyprogesterone acetate (Sekadde-Kigondu 1996),
and in Kuwait lower than for oral contraceptives (Shah 2007).
Ina randomized trial inHIVinfected women, both pregnancy and
disease progression were less common in women allocated to the
IUDthanto hormonal contraception(Stringer 2007). The copper
bearing IUD has been considered to have similar effectiveness to
injectable progestogens (Trussell 2004). The feasibility of enrolling
women into a randomized trial of IUD versus depot progestogen
contraception has been conrmed in a pilot trial conducted by
Family Health International (Feldblum 2005).
Despite an extensive literature of observational studies, there is
a shortage of high quality randomized trials comparing different
family planning methods (Helmerhorst 2006). This review will
evaluate the data available and the need for further trials.
O B J E C T I V E S
To determine, from the best available evidence, the effectiveness,
complications and continuation rates of the copper-containing
IUD compared with depot progestogen contraception.
M E T H O D S
Criteria for considering studies for this review
Types of studies
All published, unpublished and ongoing trials with random allo-
cation to IUD versus depot progestogen contraception and ade-
quate allocation concealment (see Methods of the review).
Types of participants
Women in the childbearing age group.
Potential subgroup analyses included:
- parity (nulliparous, multiparous)
- STI risk (high, low)
- HIV status (positive, negative, unknown)
- types of copper IUDs or depot progestogens (injectables, im-
plants, mixed hormonal)
Types of interventions
Copper-containing IUD compared with depot progestogen con-
traception alone or compared to mixed hormonal contraception
(including a depot progestogen).
Types of outcome measures
Primary outcomes
1. Unintended pregnancy
2. Discontinuation of the allocated method
Secondary outcomes
1. time to unintended pregnancy
2. time to discontinuation of the allocated method
3. genital tract infection (within four weeks of initiation and long-
term)
4. HIV seroconversion
5. oligo-amenorrhea
6. menorrhagia
7. dysmenorrhea
8. weight gain
9. weight loss
10. nausea/vomiting
11. surgical complications of IUD insertion (e.g. perforation of
the uterus)
12. depression
13. bone fracture
14. bone mineral density
15. stroke
16. any adverse event possibly related to contraceptive method
17. involuntary infertility after discontinuation
18. HIV disease progression
19. user satisfaction
20. provider satisfaction
21. cost
Search methods for identication of studies
We located reports using the Cochrane Fertility Regulation Group
trials search strategy.
We searched the CRG trials register, the Cochrane Central Regis-
ter of Controlled Trials (CENTRAL) (The Cochrane Library, 2009
issue), MEDLINE/PUBMED, EMBASE, LILACS and two reg-
isters of ongoing controlled trials (www.clinicaltrials.gov and the
Current Controlled Trials metaRegister).
We also searched the reference lists of identied trials.
We applied the following search strategies:
MEDLINE/PUBMED and the Cochrane Central Register of
Controlled Trials (CENTRAL):
(Intrauterine device* OR IUD* OR IUD*)
The www.clinicaltrials.gov database:
iud or iuds or IUD or intrauterine device or intrauterine devices
[ALL-FIELDS]
The Current Controlled Trials Meta Register:
(iud or iuds or IUD or IUDs or intrauterine device)
There was no language preferences for selection of trials.
Data collection and analysis
Data extraction and quality assessment
We assessed identied titles and abstracts and retrieved two full
text articles possibly eligible for inclusion. All three authors per-
formed quality assessment and agreed that both studies met the
inclusion criteria. We did not exclude any studies. Two authors
(MS, TL) carried out data extraction independently using a spe-
cially designed data extraction form. Descriptive data included:
authors, year of publication, country, time span of the trial, age
group, parity, previous contraceptive use, previous infection, HIV
status, time of enrolment (e.g. post abortion, postpartum), and
specics of the IUD and the progestogen interventions. We re-
solved disagreements between authors by consensus.
We assessed trials that met the eligibility criteria for quality using
the following criteria.
1. Generation of random allocation sequence: A = adequate, B =
inadequate, C = unclear.
2. Allocation concealment: A = adequate (such as central random-
ization; use of numbered, sealed opaque envelopes), B = unclear
whether concealment of allocation is adequate, C = inadequate
concealment of allocation (such as alternation), D = concealment
of allocation not used.
3. Blinding of participants: A = yes, B = inadequate, C = no, D =
no information.
4. Blinding of caregivers: A = yes, B = inadequate, C = no, D = no
information.
5. Blinding of outcome assessment: A = yes, B = inadequate, C =
no, D = no information.
6. Compliance with allocated intervention: A = less than 3% non-
compliance, B = 3% to 9.9% non-compliance, C = 10% or more
non-compliance, D = unclear.
7. Completeness of follow-up data (including any differential loss
of participants from each group): A = less than 3% of participants
excluded, B = 3% to 9.9% of participants excluded, C = 10% to
19.9% excluded, D = 20% or more excluded, E = unclear.
8. Analysis of participants by intention-to-treat: A = yes, B = in-
adequate, C = no, D = not clear.
Data analysis
We compared categorical data using relative risks (RR) and their
95% condence intervals (CI). We tested for statistical hetero-
geneity betweentrials using the I
2
statistic, with values greater than
50% indicating signicant heterogeneity. In the absence of sig-
nicant heterogeneity, we pooled data using a xed-effect model.
If there was signicant heterogeneity, we used a random-effects
model or didnt pool the data, and made an attempt to identify
potential sources of heterogeneity (Greenland 1994; Villar 1995)
based on subgroup analyses by specic types of contraceptives,
HIV status of participants, trial quality, and trial size. When fol-
low-up rates differed substantially, we adjusted denominators pro-
portionally to minimize bias (see Risk of bias in included studies).
R E S U L T S
Description of studies
See: Characteristics of included studies.
We identied two randomized trials comparing IUD use with de-
pot progestogen (DMPA) contraception. We have included both
in this review; together they involved 967 women. One of these
studies evaluated IUD use compared with mixed hormonal con-
traception (oral contraception or injectable depot-medroxypro-
gesterone acetate) (Stringer 2007); the other evaluated IUD com-
pared with injectable DMPA (Feldblum2005). See Characteristics
of included studies.
Settings
Both studies were conducted in developing countries: one in Zam-
bia (Stringer 2007) and the other in Brazil, Guatamala, Vietnam
and Egypt (Feldblum 2005).
Participants
Women requiring reversible, long-acting contraception. Only
HIV positive women were recruited in Stringer 2007. Subgroup
analysis was undertaken by specic types of contraceptives used.
Outcome assessments
Primary outcomes, discontinuation of allocated method and un-
intended pregnancy, were recorded as the number (%) of women
in each group in Feldblum 2005 and as women per 100 patient
years in Stringer 2007 (see Risk of bias in included studies).
Regarding our secondary outcomes, only infection and HIV dis-
ease progression were evaluated in either of these studies. PID
was assessed using CDC diagnostic criteria or Hagars criteria. In
Feldblum 2005, endocervical specimens were taken for gonorrhea
culture and chlamydia antigen. In Stringer 2007, HIVdisease pro-
gression was evaluated by CD4 counts (CD4 < 200cells/L) and
death.
Risk of bias in included studies
We considered allocation concealment adequate in both studies
(sealed, sequentially numbered, opaque envelopes). Blinding was
not possible in either due to the type of interventions (IUD inser-
tion or injections). We considered random sequence generation
adequate in both studies.
In Stringer 2007, the duration of follow up differed between the
experimental groups. The results were therefore reported as out-
comes per 100 patient years. To minimize bias, we adjusted the
denominators of the groups to compensate for the different du-
rations of follow up. We did this using the following equation:
woman-years of follow up in the group / total woman-years follow up
x total number enrolled. Whilst we acknowledge that this is not
perfectly accurate as it assumes a consistent risk of the outcome
over time which is not necessarily the case, we consider it to be a
reasonable approximation.
Also in Stringer 2007, after randomization to the hormonal group,
women were allowed to choose and to switch between oral and
injectable depot progestogen contraception and so it was not pos-
sible to compare each hormonal method separately to the IUD
group. Most women (63%) chose depot progestogen.
In Feldblum 2005, the total number of women assessed for each
outcome measure was not recorded and denominators were ex-
pressed as the total number enrolled. After contacting the authors,
we decided, for this review, to exclude those women lost to follow
up in each group.
Effects of interventions
Based on the limited data of these two studies, the IUD is more
effective than depot progestogens at preventing pregnancy (risk
ratio (RR) 0.45; 95% condence interval (CI) 0.24 to 0.84).
Regarding rates of discontinuation of contraception method,
Feldblum 2005 had a higher discontinuation rate in the depot
group and Stringer 2007 had a higher discontinuation rate in the
IUD group.
HIV positive participants in Stringer 2007 were less likely to ex-
perience HIV/AIDS disease progression (including death) in the
IUD group than in the depot progestogen group (RR 0.58; 95%
CI 0.39 to 0.87) (Figure 1, Figure 2).
Figure 1. Forest plot of comparison: 1 IUD versus DMPA, outcome: 1.4 HIV disease progression: CD4<200.
Figure 2. Forest plot of comparison: 1 IUD versus DMPA, outcome: 1.5 HIV disease progression (CD4<200
or death).
The incidence of PIDwas lowin both groups and not signicantly
different.
D I S C U S S I O N
The twostudies includedinthe reviewwere consistent withrespect
to the nding of fewer pregnancies in women allocated to IUD
versus hormonal contraception.
This review found a disparity in discontinuation rates between
studies that could be due to a difference in method acceptability
in the different populations of women studied. However it is also
possible that women in the Stringer 2007 study were less likely
to discontinue the hormonal contraception as, if they were dissat-
ised with one hormonal method, they were given the option of
switching to an alternative hormonal method.
Since mixed hormonal contraception was used in Stringer 2007,
it is possible that the effect on HIV disease progression was due
mainly to the depot progestogen or mainly to the oral contra-
ceptive pill or due to both. A secondary analysis of their data in
Stringer 2009 suggests the latter. As the nding of reduced disease
progression with the IUD was not based on a prior hypothesis,
the nding needs to be conrmed in a new study.
A U T H O R S C O N C L U S I O N S
Implications for practice
This review has found a lower rate of pregnancy in women allo-
cated to the IUD versus hormonal contraception. This informa-
tion will be useful for counselling women regarding their choice
of contraception. The importance of choice and the option to
change methods is suggested (though indirectly) by the fact that
discontinuation of hormonal contraception relative to the IUD
was less in the study in which women were allowed to choose and
change between different hormonal contraception methods. HIV
positive women should be given the option of using an IUDwhile
we await the results of larger trials comparing long term contra-
ception methods.
Implications for research
The studies reviewed had a limited range of outcomes and rela-
tively small sample sizes. Further research should investigate other
outcomes such as bone density (especially in the context of HIV),
depression, weight gain, dysmenorrhoea, menorrhagia and user
satisfaction. Highly important, in the light of the data in this re-
view, is the need for large trials to investigate the impact of these
contraception methods on HIV acquisition/seroconversion and
HIV disease progression.
A C K N O W L E D G E M E N T S
We thank the trial authors who have contributed additional in-
formation for this review, and the Cochrane Fertility Regulation
Group for technical support.
R E F E R E N C E S
References to studies included in this review
Feldblum 2005 {published data only}
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Morales Eet al. Randomized assignment to copper IUD or depot-
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18791.
Stringer 2007 {published data only}
Stringer EM, Kaseba C, Levy J, Sinkala M, Goldenberg RL, Chi
BH, et al.A randomized trial of the intrauterine contraceptive
device vs hormonal contraception in women who are infected with
the human immunodeciency virus.. American Journal of Obstetrics
and Gynecology 2007 Aug;197(2):144.e18.
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Indicates the major publication for the study

C H A R A C T E R I S T I C S O F S T U D I E S
Characteristics of included studies [ordered by study ID]
Feldblum 2005
Methods 368 sexually active women randomized to receive a copper IUD or depot-medroxyprogesterone acetate.
Participants Women attending family planning clinics in Brazil, Guatamala, Egypt and Vietnam included if sexually
active, requiring contraception and willing to use either IUD or DMPA for a period of at least a year.
Excluded if medical contraindications to IUD or DMPA; pregnancy; suspected of having a current STI;
currently using an IUD; DMPA injection within the past 6 months.
Interventions IUD (TCu 380A) inserted or 3-monthly injections of 150mg DMPA.
Outcomes PIDusing CDCdiagnostic criteria; STIs namely gonorrhea (endocervical specimenculture) and chlamydia
(Antigen).
Notes Study was stopped after one year due to the fact that it was mainly a feasibility study. At this time, only
32% of women had completed 12 months. Loss to follow up at trial closure was 17.9%.
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes Sequentially numbered, sealed, opaque envelopes
were used.
Stringer 2007
Methods 599 HIV-infected women randomized to IUD or mixed hormonal contraception and followed up for at
least two years.
Participants HIV-infected postnatal women attending two primary clinics in Lusaka, Zambia. Included if at least
sixteen years old, desired contraception for at least two years, and reported two or less sexual partners
in the previous year. Excluded if advanced HIV disease (WHO stage III or IV), a history of a bleeding
disorder, a history of PID within previous 5 years or < 16 years old.
Interventions IUD (TCu 380A) or hormonal contraception (either DMPA (150mg) or the OCP offered). If OCP,
levonorgestrel 0.03mg/d only for six months, then switched to the COCP with levonorgestrel 0.15mg
and estradiol 0.03mg/d).
Outcomes Pregnancy (hCG), PID (Hagars criteria), method discontinuation, clinical disease progression (death,
CD4 and FBC).
Stringer 2007 (Continued)
Notes The trial suffered quite a high loss to follow up (68% in the OC group and 77% in the IUD group),
recorded as patient years that differed signicantly between the two groups. To avoid bias (as would be
the case if we used the rawnumber originally allocated as the denominator), we adjusted the denominators
to compensate for the different durations of followup. We did this using the following equation: woman-
years of follow up in the group / total woman-years follow up x total number enrolled. Whilst we acknowledge
that this is not perfectly accurate, as it assumes a consistent risk of the outcome over time which is not
necessarily the case, we consider this to be a reasonable approximation.
Risk of bias
Item Authors judgement Description
Allocation concealment? Yes Sequentially numbered opaque envelopes were
used.
CD4: cluster of differentiation 4
COCP: combined oral contraceptive pillDMPA: depot medroxyprogesterone acetate
FBC: full blood count
IUD: intrauterine device
OC: oral contraceptive
OCP: oral contraceptive pill
PID: pelvic inammatory disorder
STI: sexually transmitted infection
D A T A A N D A N A L Y S E S
Comparison 1. IUCD versus depot progestogen
Outcome or subgroup title
No. of
studies
No. of
participants
Statistical method Effect size
1 Pregnancy 2 937 Odds Ratio (M-H, Fixed, 95% CI) 0.45 [0.24, 0.84]
1.1 IUCD vs depot
progestogen
1 338 Odds Ratio (M-H, Fixed, 95% CI) 0.5 [0.09, 2.77]
1.2 IUCD versus mixed
hormonal contraception (depot
progestogen and/or OC)
2 Discontinuation of allocated
method
2 Odds Ratio (M-H, Fixed, 95% CI) Subtotals only
2.1 IUCD vs depot
progestogen
3 HIV disease progression: CD4 <
200
3.1 IUCD vs depot
progestogen
0 0 Odds Ratio (M-H, Fixed, 95% CI) Not estimable
4 HIV disease progression: death 1 599 Odds Ratio (M-H, Fixed, 95% CI) 0.69 [0.33, 1.44]
5 HIV disease progression (CD4 <
200 or death)
6 Pelvic inammatory disease 2 937 Odds Ratio (M-H, Fixed, 95% CI) 3.90 [0.44, 34.91]
6.1 IUCD vs depot
progestogen
Analysis 1.1. Comparison 1 IUCD versus depot progestogen, Outcome 1 Pregnancy.
Review: Copper containing intra-uterine devices versus depot progestogens for contraception
Comparison: 1 IUCD versus depot progestogen
Outcome: 1 Pregnancy
Study or subgroup Experimental Control Odds Ratio Weight Odds Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 IUCD vs depot progestogen
Feldblum 2005 2/168 4/170 12.7 % 0.50 [ 0.09, 2.77 ]
Subtotal (95% CI) 168 170 12.7 % 0.50 [ 0.09, 2.77 ]
Total events: 2 (Experimental), 4 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.79 (P = 0.43)
2 IUCD versus mixed hormonal contraception (depot progestogen and/or OC)
Stringer 2007 14/314 27/285 87.3 % 0.45 [ 0.23, 0.87 ]
Subtotal (95% CI) 314 285 87.3 % 0.45 [ 0.23, 0.87 ]
Total (95% CI) 482 455 100.0 % 0.45 [ 0.24, 0.84 ]
Heterogeneity: Chi
2
= 0.01, df = 1 (P = 0.90); I
2
=0.0%
0.01 0.1 1 10 100
Favours experimental Favours control
Analysis 1.2. Comparison 1 IUCD versus depot progestogen, Outcome 2 Discontinuation of allocated
method.
Outcome: 2 Discontinuation of allocated method
Feldblum 2005 6/168 36/170 100.0 % 0.14 [ 0.06, 0.34 ]
Subtotal (95% CI) 168 170 100.0 % 0.14 [ 0.06, 0.34 ]
Stringer 2007 146/286 38/313 100.0 % 7.55 [ 5.00, 11.38 ]
Subtotal (95% CI) 286 313 100.0 % 7.55 [ 5.00, 11.38 ]
Test for overall effect: Z = 9.64 (P < 0.00001)
0.01 0.1 1 10 100
Analysis 1.3. Comparison 1 IUCD versus depot progestogen, Outcome 3 HIV disease progression: CD4 <
200.
Outcome: 3 HIV disease progression: CD4 < 200
Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]
Test for overall effect: not applicable
Stringer 2007 41/282 56/256 100.0 % 0.61 [ 0.39, 0.95 ]
Subtotal (95% CI) 282 256 100.0 % 0.61 [ 0.39, 0.95 ]
Total (95% CI) 282 256 100.0 % 0.61 [ 0.39, 0.95 ]
0.01 0.1 1 10 100
Analysis 1.4. Comparison 1 IUCD versus depot progestogen, Outcome 4 HIV disease progression: death.
Outcome: 4 HIV disease progression: death
Stringer 2007 13/313 17/286 100.0 % 0.69 [ 0.33, 1.44 ]
Total (95% CI) 313 286 100.0 % 0.69 [ 0.33, 1.44 ]
0.01 0.1 1 10 100
Analysis 1.5. Comparison 1 IUCD versus depot progestogen, Outcome 5 HIV disease progression (CD4 <
200 or death).
Outcome: 5 HIV disease progression (CD4 < 200 or death)
Stringer 2007 52/315 72/284 100.0 % 0.58 [ 0.39, 0.87 ]
Total (95% CI) 315 284 100.0 % 0.58 [ 0.39, 0.87 ]
0.01 0.1 1 10 100
Analysis 1.6. Comparison 1 IUCD versus depot progestogen, Outcome 6 Pelvic inammatory disease.
Outcome: 6 Pelvic inammatory disease
Feldblum 2005 2/168 0/170 48.5 % 5.12 [ 0.24, 107.45 ]
Subtotal (95% CI) 168 170 48.5 % 5.12 [ 0.24, 107.45 ]
Stringer 2007 1/313 0/286 51.5 % 2.75 [ 0.11, 67.79 ]
Subtotal (95% CI) 313 286 51.5 % 2.75 [ 0.11, 67.79 ]
Total (95% CI) 481 456 100.0 % 3.90 [ 0.44, 34.91 ]
Heterogeneity: Chi
2
= 0.08, df = 1 (P = 0.78); I
2
=0.0%
0.01 0.1 1 10 100
H I S T O R Y
Protocol rst published: Issue 2, 2008
Review rst published: Issue 6, 2010
9 November 2009 Amended new author added
13 October 2009 Amended Submission draft completed
27 August 2009 Amended First draft of review completed
19 April 2008 Amended Converted to new review format.
3 December 2007 New citation required and major changes Substantive amendment
C O N T R I B U T I O N S O F A U T H O R S
GJH prepared the rst draft of the protocol. MS reviewed the draft. GJH, MS and TL extracted data. TL prepared the rst draft of
the review, which was contributed to by GJH and MS.
D E C L A R A T I O N S O F I N T E R E S T
Two authors (MS and GJH) are proposing to undertake a randomized trial of IUD versus depot progestogen contraception. Any
decision related to the inclusion of this trial in the review will be taken by TL and an independent expert, such as a Review Group
editor.
S O U R C E S O F S U P P O R T
Internal sources
(GJH) Effective Care Research Unit, University of the Witwatersrand, University of Fort Hare, Eastern Cape Department of
Health, South Africa.
(MS) Effective Care Research Unit, University of the Witwatersrand, University of Fort Hare, Eastern Cape Department of
Health, South Africa.
External sources
UNDP/UNFPA/WHO/World Bank (HRP, Switzerland.
D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W
Reference to articles by Morrison 2009 and Myer 2007 have been included in the background of the review. Under Methods, we have
added women using mixed hormonal contraception to the subgroup analyses.

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